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pMMLV-CAR Mesothelin (YP218) h(BBζ) (CAR-MV-01LX293)

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All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Recombinant Moloney murine leukemia virus (MMLV) retroviral vectors serve as efficient viral vector tools for introducing genes permanently into a wide variety of dividing cells, and provide an alternative to modify primary T cells. Creative biolabs has developed retroviral CAR vector pMMLV Mesothelin (YP218) h(BBζ), which is constructed for the engineering of T cells to target human Mesothelin. The T cells are genetically modified through transduction with a retroviral vector expressing scFv of anti-Mesothelin antibody linked to CD137 (4-1BB) and CD3-zeta signaling domains. And the vector product was designed for the treatment of Neuroblastoma.

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Details

  • Target
  • Mesothelin
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • Neuroblastoma
  • Generation
  • Second
  • Vector Name
  • pMMLV
  • Vector Length
  • ~6kb
  • Vector Type
  • Recombinant Moloney murine leukemia virus (MMLV) retroviral vector
  • Receptor Construction
  • scFv-41BB-CD3ζ
  • Discription of Signaling Cassetes
  • 41BB
    CD137 (also known as 4-1BB) is a surface co-stimulatory glycoprotein originally described as present on activated T lymphocytes, which belongs to the tumor necrosis factor (TNF) receptor superfamily. It is expressed mainly on activated CD4+ and CD8+ T cells, and binds to a high-affinity ligand (4-1BBL) expressed on several antigen-presenting cells such as macrophages and activated B cells. On the basis of preclinical observation, this molecule can promote the persistence of antigen-specific and antigennonspecific chimeric antigen receptor T-cells to significantly increases antitumor activity.
    CD3ζ
    CD3ζ, also known as T-cell receptor zeta, which together with T-cell receptor and CD3γ, δ, ε chain, forms the TCR-CD3 complex. ζ was expressed independently from the complex. The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. CD3-zeta, which contains 3 ITAMs, is the most commonly used endodomain component of CARs. It transmits an activation signal to the T cell after antigen is bound. CD3-zeta may not provide a fully competent activation signal and additional co-stimulatory signaling is needed. For example, chimeric 4-1BB and OX40 can be used with CD3-zeta to transmit a proliferative/survival signal, or all three can be used together.

Target

  • Clone
  • YP218
  • Host
  • Humanized
  • Target Species
  • Human
  • Gene Name
  • mesothelin
  • Synonyms
  • Mesothelin;MSLN; mesothelin; MPF; SMRP;

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  • Published Data
CAR scFv data IHC

Fig.1 Examples of YP218 antibody reactivity to normal human tissues by IHC.

CAR Construction : Latest CAR Construction

Fig.1 Examples of YP218 antibody reactivity to normal human tissues by IHC.

Shown are representative staining of normal mesothelial cells that express mesothelin while as normal tissues of liver, lung, and kidney are negative for mesothelin expression.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
CAR scFv data FCM

Fig.2 Cell surface mesothelin expression on human tumor cell lines by flow cytometry using YP218.

CAR Construction : Latest CAR Construction

Fig.2 Cell surface mesothelin expression on human tumor cell lines by flow cytometry using YP218.

MSLN expression indicated as + or -. A431-H9 is the A431 epidermoid carcinoma cell line transduced for high expression of human mesothelin.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.3 In vitro anti-tumor activity of hYP218 and SS1 CAR T cells.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.3 In vitro anti-tumor activity of hYP218 and SS1 CAR T cells.

Killing of mesothelin-expressing OVCAR-8 cells upon co-culture with untransduced, SS1 CAR or hYP218 CAR T cells at different Effector to Target ratios (E:T).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.4 Percent killing of different mesothelin-expressing tumor cells upon co-culture with SS1 CAR or hYP218 CAR T cells at E:T of 3.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.4 Percent killing of different mesothelin-expressing tumor cells upon co-culture with SS1 CAR or hYP218 CAR T cells at E:T of 3.

Mesothelin-negative cell lines A431, KLM1 MSLN k/o and H1703 were used as negative controls. hYP218-CAR (Red), SS1-CAR (Grey).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.5 Release of cytokines IFN-γ upon co-culture of tumor cells with hYP218 CAR T cells.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.5 Release of cytokines IFN-γ upon co-culture of tumor cells with hYP218 CAR T cells.

hYP218-CAR (Red), SS1-CAR (Grey).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.6 Release of cytokines IL-2 upon co-culture of tumor cells with hYP218 CAR T cells.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.6 Release of cytokines IL-2 upon co-culture of tumor cells with hYP218 CAR T cells.

hYP218-CAR (Red), SS1-CAR (Grey).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.7 Release of cytokines TNF-α upon co-culture of tumor cells with hYP218 CAR T cells.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.7 Release of cytokines TNF-α upon co-culture of tumor cells with hYP218 CAR T cells.

hYP218-CAR (Red), SS1-CAR (Grey).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.8 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.8 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

Bioluminescence imaging (BLI) of OVCAR-8 tumor growth in NSG mice treated with CAR T cells, red arrow indicates CAR T cell infusion on day 14 after tumor
implantation.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.9 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.9 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

Kinetics of OVCAR-8 tumor growth.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.10 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.10 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

Overall survival of OVCAR-8 tumor implanted mice in different treatment groups.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.11 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.11 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

Bioluminescence imaging (BLI) of KLM-1 tumor growth in NSG mice treated with CAR T cells, red arrow indicates CAR T cell infusion on day 14 after tumor
implantation.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.12 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.12 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

Kinetics of KLM-1 tumor growth.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.13 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.13 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

Overall survival of KLM-1 tumor implanted mice in different treatment groups.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.14 Anti-tumor efficacy of hYP218 and SS1 CAR T cells using a mesothelioma patient derived cell line xenograft model.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.14 Anti-tumor efficacy of hYP218 and SS1 CAR T cells using a mesothelioma patient derived cell line xenograft model.

Killing of mesothelioma patient-derived NCI-Meso63 tumor cells upon co-culture with autologous untransduced, SS1 CAR or hYP218 CAR T cells derived from the PBMCs from the same patient at different E:T ratios.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.15 Anti-tumor efficacy of hYP218 and SS1 CAR T cells using a mesothelioma patient derived cell line xenograft model.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.15 Anti-tumor efficacy of hYP218 and SS1 CAR T cells using a mesothelioma patient derived cell line xenograft model.

Kinetics of NCI-Meso63 mesothelioma tumor growth in mice implanted with subcutaneous NCI-Meso63 cells. CAR T cells were infused on day 14 after tumor implantation.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.16 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.16 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

Representative FCM analysis (n = 1 mouse) detecting the presence of hCD45+hCD3+ double-positive human T cells in the blood (left panel) and tumors (central panel) of NSG mice implanted with KLM-1 tumors, on days 2 and day 7 after CAR T cell infusion.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.17 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.17 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

Change in the number of hCD45+ hCD3+ human T cells in 100 mcL blood from day 2 to day 7 after CAR T cell infusion (n=3). hYP218-CAR (Red), SS1-CAR (Grey).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.18 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.18 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

Change in the percentage of tumor infiltrating hCD45+hCD3+ human T cells from day 2 to day 7 after CAR T cell infusion (n=3).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data FCM

Fig.19 hYP218 CAR T cell therapy provides anti-tumor immunity.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.19 hYP218 CAR T cell therapy provides anti-tumor immunity.

Representative flow cytometry of peripheral blood cells obtained from a mouse with KLM-1 tumor that was treated with hYP218 CAR T cells and stained with hCD45, hCD3 and hEGFR to detect hYP218 CAR T cells.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.20 hYP218 CAR T cell therapy provides anti-tumor immunity.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.20 hYP218 CAR T cell therapy provides anti-tumor immunity.

In vivo imaging measured in photons/second in age matched untreated mice as well as mice previously treated with hYP218 CAR T cells.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.
Complete CAR data Funcs

Fig.21 hYP218 CAR T cell therapy provides anti-tumor immunity.

CAR Construction : hYP218 scfv-41BB-CD3ζ Latest CAR Construction

Fig.21 hYP218 CAR T cell therapy provides anti-tumor immunity.

In vivo total radiance measured in photons/second in age matched untreated mice as well as mice previously treated with hYP218 CAR T cells.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

More Published Data More Published Data

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For research use only. Not intended for any clinical use. No products from Creative Biolabs may be resold, modified for resale or used to manufacture commercial products without prior written approval from Creative Biolabs.

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